Challenges to the processes of sleep-wake cycle regulation in aging

在20岁到60岁之间，年龄的增长与睡眠时间的减少、睡眠中的觉醒时间、深度睡眠的减少以及睡眠的较浅阶段有关。我们计划的长期目标是了解睡眠-觉醒周期与年龄相关变化背后的机制。睡眠和警觉的质量是由体内平衡过程(清醒的小时数)和昼夜节律过程(来自生物钟的信号)之间的相互作用控制的。衰老可能会单独或当它们相互作用时对这些过程产生负面影响。我们的方法是评估年龄对挑战对动态平衡和昼夜节律过程的影响的贡献。具体地说，我们将评估与睡眠动态平衡相关的药物操作的年龄相关效应。我们之所以选择咖啡因，是因为它是一种与睡眠稳态密切相关的神经调节剂(腺苷)的拮抗剂。目的是：(1)绘制衰老过程中睡眠稳态调节的剂量-反应曲线。我们将评估三种剂量的咖啡因对年轻人和老年人的影响。我们预计，随着剂量的增加，与年龄相关的差异将会加强。我们还将评估习惯性摄入咖啡因对与年龄相关的咖啡因影响。我们预计，与年龄相关的差异在低咖啡因消费者中会比在高咖啡因消费者中更加明显。(2)评估动态平衡和昼夜节律过程之间的相互作用如何调节衰老中的睡眠/保持清醒的能力。我们将比较咖啡因在一天中的不同时间段以及在睡眠-醒来周期的时间发生变化时(比如在时差中)对年龄的影响。我们预计，当睡眠-觉醒周期发生在一天中的不正常时间时，咖啡因的影响和与年龄相关的差异将更加突出。(3)评估衰老过程中动态平衡睡眠驱动力减弱对警觉的影响。我们将通过咖啡因对年龄较大和年龄较小的受试者睡眠的不利影响来评估咖啡因对警觉性的“间接”影响。我们预计，当睡眠受到更多影响时(即不正常的时间安排、年龄较大的受试者)，间接影响会更加突出。这个程序将为衰老如何改变睡眠-觉醒周期提供重要线索。

Between the ages of 20 and 60, increasing age is associated with less time asleep, more awakenings during sleep, less deep sleep, and more lighter stages of sleep. The long term goal of our program is to understand the mechanisms that underlie age-related changes of the sleep-wake cycle. The quality of sleep and vigilance is controlled by the interaction between the homeostatic process (number of hours of wakefulness) and the circadian process (signal from the biological clock). Aging may have a negative impact on these processes individually or when they interact.  Our approach is to evaluate the contribution of age to the effects of challenges put on homeostatic and circadian processes. Specifically, we will evaluate age-related effects of pharmacological manipulations associated to sleep homeostasis. We have selected caffeine because it is an antagonist of a neuromodulator closely related to sleep homeostasis (adenosine). Objectives are: (1) To perform a dose-response curve of manipulations of sleep homeostasis in aging. We will evaluate the effects of three doses of caffeine in young and older subjects. We expect age-related differences to be enhanced following higher doses.We will also evaluate the impact of habitual caffeine consumption on age-related effects of caffeine. We expect age-related differences to be more pronounced in low caffeine consumers than in high consumers. (2) To assess how interactions between homeostatic and circadian processes modulate the ability to sleep/stay awake in aging. We will compare age-related effects of caffeine at different times of day as well as when submitted to a shift in the timing of the sleep-wake cycle (like in jet-lag). We expect caffeine's effects and age-related differences to be more prominent when the sleep-wake cycle occurs at an abnormal time of day. (3) To evaluate the consequences on vigilance of an attenuation of homeostatic sleep drive in aging. We will evaluate the "indirect" effects of caffeine on vigilance through its detrimental effects on sleep in older and younger subjects. We expect indirect effects to be more prominent when sleep is more affected (i.e. abnormal timing, older subjects). This program will privide important cues on how aging modifies the sleep-wake cycle.